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Two‐stage exposure of Syrian‐hamster‐embryo cells to environmental carcinogens: superinduction of ornithine decarboxylase correlates with increase of morphological‐transformation frequency
Author(s) -
Dhalluin Stéphane,
Elias Zoé,
Cruciani Véronique,
Bessi Halima,
Poirot Odile,
Rast Claudine,
Gate Laurent,
Pages Nicole,
Tapiero Haim,
Vasseur Paule,
NguyenBa Giao
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980302)75:5<744::aid-ijc13>3.0.co;2-6
Subject(s) - carcinogen , ornithine decarboxylase , hamster , chemistry , carcinogenesis , benzo(a)pyrene , biology , medicine , endocrinology , biochemistry , enzyme , gene
As part of environmental toxicology, it is important to assess both the carcinogenic potential of xenobiotics and their mode of action on target cells. Since dysregulation of ornithine decarboxylase (ODC), a rate‐limiting enzyme of polyamine biosynthesis, is considered as an early and essential component in the process of multistage carcinogenesis, we have studied the mode of ODC induction in Syrian‐hamster‐embryo(SHE) cells stage‐exposed to carcinogens and to non‐carcinogens. One‐stage (5 hr) treatment of SHE cells with 50 μM clofibrate (CLF), a non‐genotoxic carcinogen, or with 0.4 μM benzo(a)pyrene (BaP), a genotoxic carcinogen, slightly decreased basal ODC activity. Using the 2‐stage exposure, 1 hr to carcinogen, then replacement by TPA for 5 hr, the ODC activity was higher than that obtained with TPA alone. This ODC superinduction was not observed when SHE cells were similarly pre‐treated with non‐carcinogenic compounds. Several environmental chemicals, pesticides, solvents, oxidizers and drugs were investigated with this SHE cell model. With one‐stage exposure, some xenobiotics decreased basal ODC activity, while for others ODC changes were not noticeable. With 2‐stage exposure (chemical followed by TPA), all carcinogens amplified the TPA‐inducing effect, resulting in ODC superinduction. Comparative studies of the action of carcinogens and of non‐carcinogens, using 2‐stage exposure protocols, clearly show a close relationship between ODC induction rate and morphological transformation frequency. Int. J. Cancer 75:744–749, 1998.© 1998 Wiley‐Liss, Inc.